Coating composition, coating and an object coated with the coating composition

ABSTRACT

A process for producing a coating composition includes separately chemically grafting particles with compounds having reactive groups and compounds having hydrophilic polymer chains. The hydrophilic polymer chains dissolve in water at least one temperature between 0 and 100° C. The reactive groups may react with the substrate and or react with one another to form a cross-linked coating, comprising the particles. A process for forming a coating on a substrate is also provided.

This application is a divisional of commonly owned U.S. application Ser.No. 11/659,511, filed Jul. 26, 2008 (now abandoned), which is thenational phase application under 35 USC §371 of PCT/NL2005/000486 filedJul. 7, 2005 which designated the U.S. and claims benefit of EP04077284.0, filed Aug. 10, 2004, the entire contents of each of whichare hereby incorporated by reference.

The invention relates to a coating composition and a coating comprisinga hydrophilic polymer, a device coated with the coating composition andparticles for use in the coating composition.

Coating compositions comprising hydrophilic polymers are applied ondifferent objects, to give all kind of properties to those objects. Itis possible that the coating composition is applied to objects with thepurpose to suppress or prevent biofouling. Objects made of syntheticmaterials in contact with water are generally prone to suffer fromundesired accumulation of biologically derived organic species, alsoreferred to as biofouling, be it by example protein adsorption,bacterial adsorption and subsequent spreading, or thrombosis. Thisundesired accumulation has serious consequences; for example, in themedical area bacterial infections via catheters may be caused by theaccumulation and in industry the clogging of filters, accumulation oforganic material on surfaces etc also causes problems.

Grafting hydrophilic polymer chains to the surface of the articles madeof the synthetic materials has been seen as a manner to decrease or evento prevent biofouling.

It is also possible that that such a coating containing hydrophilicpolymers also comprises specific additives, like for example therapeuticspecies. Also specific functional groups may be adehered to thehydrophilic polymers or otherwise incorporated into the coating, to makethe coating for example bioreactive, for example to bind anti-bodies,cell receptors, enzymes etc.

A coating composition and a coating comprising hydrophilic polymerchains is known from S. J. Sophia, et al, Macromolecules 31, 5059(1998). The coating is obtained by grafting to a surface hydrophilicpolymer chains to obtain a coating comprising hydrophilic polymerchains, by using hydrophilic polymer chains with one reactive group thatreact with the reactive groups in the surface. However the thickness ofthe layer of grafted hydrophilic polymers is limited to only a fewmolecules. Therefore the layer has insufficient mechanical robustnessand is easily damaged, so that antibiofouling properties are lost. Afurther disadvantage is that that the processing is laborious, i.e. thechemical grafting of groups often necessitates an extra treatment of thesurface to make the reaction feasible. Yet a further problem is that theanti-biofouling properties are insufficient.

Another method is using Langmuir Blodgett technique to transferhydrophilic chains to a surface, optionally grafting them afterwards, asdescribed in E. P. K. Currie et al, Applied Chem. 71, 1227 (1999).However this process is time consuming and it is only suitable forbatch-wise processes and specific substrates. A further problem is thatthe anti-biofouling properties are not optimal and again the mechanicalrobustness of such a coating is insufficient.

Yet another method is to use a cross-linked coating comprising reactivepolymers. These can be either linear polymers crosslinked in situ byelectron beam, as described in P. Krsko et al, Langmuir 19, 5618 (2003)or starlike polymers which crosslink via e.g. isocyante groups. Thisresults in hydrogel coatings which have protein repellant properties,are lubricious but lack mechanical robustness.

In DE-10239762 a composition nanoparticles having poly-propyleneglycolsulfogroups on their surface is disclosed. In this case no hydrophilicpolymer chains are used, since the water solubility is obtained by theionic —SO3Na group and not by the polypropyleneglycol chains, so thatthe composition is not suitable for anti-fouling applications.Furthermore the particles are very complicated to produce and there areno or only limited possibilities to change the composition of theparticles to optimise the composition with respect to its intended use.

Aim of the present invention is to provide a coating compositioncomprising a hydrophilic polymer, which may be applied to variousobjects having all kind of functions.

Surprisingly this object is obtained by a coating composition comprisingparticles being chemically grafted with reactive groups and hydrophilicpolymers.

A further advantage of the resulting coating shows good mechanicalproperties, like hardness and scratch resistance.

Yet a further advantage is that the coating shows good anti-biofoulingproperties.

Yet another advantage is that the coating shows good anti-foggingproperties.

Yet a further advantage is that the coating shows a good adhesion tosubstrates.

Yet a further advantage is that the coating may have good lubriciousproperties.

Yet a further advantage is that the coating can be designed to bebioreactive, by grafting specific groups to the surface of theparticles, or incorporating them in the network formed by said reactiveparticles.

Yet another advantage of the coating composition is its optical clarity,especially in the dry state.

Particles

The coating composition may comprise all kind of particles, as long asthe particles are grafted with the reactive groups and the hydrophilicpolymer chains. It is possible that the coating composition comprisesorganic and/or inorganic particles. Examples of organic particles arecarbon nano tubes or carbon nano spheres. Preferably the coatingcomposition comprises inorganic particles, because in this way a verystrong coating is obtained. Preferably the average largest diameter ofthe particles is less than 10 micron, preferably less than 1 micron.Still more preferably the average largest diameter of the particles isless than 100 nm, still more preferably less than 50 nm. This is becausethis provides a very strong coating, having a smooth surface. It is alsopossible with particles of these very small diameters to provide atransparent coating.

In the case of spherical particles there is only one diameter toconsider, so that the diameter is equal to the smallest diameter. Fornon-spherical particles (for instance but not limited to rods andplatelets) the largest diameter is measured as the largest straight linedrawn across the particle. Methods for determining the particledimensions include optical microscopy, scanning microscopy and atomicforce microscopy (AFM). If a microscopical method is used the dimensionsof 100 randomly chosen particles are measured and the average iscalculated. Examples of suitable inorganic particles are particles thatcomprise SiO2, TiO2, ZnO2, TiO2, SnO2, Am—SnO2, ZrO2, Sb—SnO2, Al2O3, Auor Ag.

Hydrophilic Polymers

It is possible that the particles are grafted with all kind ofhydrophilic polymer chains. A hydrophilic polymer chain is a polymerchain that dissolves in water at at least one temperature between 9 and100° C. Preferably a polymer is used that dissolves in water in atemperature range between 20 and 40° C. Preferably the hydrophilicpolymer dissolves for at least 0.1 gram per liter of water, morepreferably for at least 0.5 grams per liter, most preferably for atleast 1.0 gram per liter. For determining the solubility in water thepolymer chains are taken not comprising the groups for grafting thepolymer chains or any other group that is attached to the polymer afterthe polymerisation, for example an ionic group. Preferably thesolubility is determined in water having a pH of between 3 and 10, morepreferably in between 5.5 and 9, most preferably having a pH of 7.

The polymer chain may comprise one monomer species (homopolymer), ormore species (copolymer) arranged in a random manner or in orderedblocks.

Preferably the hydrophilic polymer chains comprise monomer units ofethylene oxide, (meth)acrylic acid, (meth)acrylamide, vinylpyrrolidone,2-hydroxyethyl(meth)acrylate, phosphorylcholine, glycidyl(meth)acrylateor saccharides.

One of the typical advantages that the coating imparts to the coatedobject are very good anti-biofouling properties of the coating,resulting from the hydrophilicity of the polymer chain. These propertiesincrease with increasing concentration and length of hydrophilic polymerchain at the surface of the coating.

Preferably the chains of the hydrophilic polymer comprise at least anaverage of 5 monomeric units, more preferably the polymer comprises atleast an average of 7 monomeric units, still more preferably the polymercomprises at least an average of 10 monomeric units, most preferably thepolymer comprises at least an average of 15 monomeric units.

The concentration may for example be increased by increasing the densityof grafted polymers to the particles, increasing the length, or byincreasing the weight ratio of the particles in the coating composition.

For obtaining good anti-fogging properties polymer chains having arelatively short length are preferred.

Another advantage of the coating composition is a low static watercontact angle. Preferably the static water contact angle is below 50°,more preferably below 40°, still more preferably below 30°.

Groups Used for Grafting

Groups for grafting the hydrophilic polymer chains and compoundscomprising the reactive groups to the particles may comprise all groupsknown in the art for grafting, for instance but not limited to(trialkoxy)silanes, thiols, amines, silane hydrides. Due to the graftingreaction the hydrophilic polymer chains and the compounds comprising thereactive groups are chemically bounded to the surface of the particles.It is possible that the hydrophilic polymers and the compoundscomprising the reactive group comprise more than one group for graftingper molecule. In a more preferred embodiment the hydrophilic polymersand the compounds reactive groups have on average one group for graftingper molecule. In case of the hydrophilic polymer the group for graftingpreferably is an endgroup attached to the chain of the hydrophilicpolymer.

Reactive Groups.

As reactive groups groups are used that may react with the substrateand/or react to form a cross-linked phase so to form a coatingcomprising the particles. It is possible that a single species ofreactive groups is used, able to mutually react, for example in a homopolymerisation reaction. Examples of such reactive groups includeacrylate and methacrylate groups. Another possibility is that a mixtureof groups is used, for example groups that are able to react in acopolymerisation reaction. Examples of such groups include carboxylicacids and/or carboxylic anhydrides combined with epoxies, acids combinedwith hydroxy compounds, especially 2-hydroxyalkylamides, amines combinedwith isocyanates, for example blocked isocyanate, uretdion orcarbodiimide, epoxies combined with amines or with dicyandiamides,hydrazinamides combined with isocyanates, hydroxy compounds combinedwith isocyanates, for example blocked isocyanate, uretdion orcarbodiimide, hydroxy compounds combined with anhydrides, hydroxycompounds combined with (etherified) methylolamide (“amino-resins”),thiols combined with isocyanates, thiols combined with acrylates orother vinylic species (optionally radical initiated), acetoacetatecombined with acrylates, and when cationic crosslinking is used epoxycompounds with epoxy or hydroxy compounds. Addition reactions such as2+2 photo cyclo addition and 4+2 thermal additions are also possible.

It is also possible that reactive groups are attached to the hydrophilicpolymer chains, however preferably at least 20 wt. % of the hydrophilicpolymer chains do not comprise such a reactive group. More preferably atleast 50 wt. %, still more preferably at least 80 wt. % of thehydrophilic polymer chains do not comprise such a reactive group. Mostpreferably the hydrophilic polymer chains do not comprise any of suchreactive groups at all.

Reactive Diluents

The coating composition may comprise one or more reactive diluents,defined as a compound that has at least one group capable of reactingmutually and or capable of reacting with the reactive groups grafted tothe particles.

In principle a wide variety of compounds are suitable to be used as thereactive diluent, for example monomers or oligomers having the samegroups as the reactive groups as defined above. In a preferredembodiment, these reactive diluents are water soluble in the sametemperature range as the grafted hydrophilic polymer.

Possible compounds that may be used as the reactive diluent areisocyanates, alkoxy titanates, alkoxy zirconates, or urea-,urea/melamine-, melamine-formaldehyde or phenol-formaldehyde (resol,novolac types), or radical curable (peroxide- or photo-initiated)unsaturated mono- and polyfunctional monomers and polymers, e.g.acrylates, methacrylates, maleate/vinyl ether), or radical curable(peroxide- or photo-initiated) unsaturated e.g. maleic or fumaric,polyesters in styrene and/or in methacrylates.

Method for Crosslinking.

Any cross-linking method that may cause the reactive groups to react andso to form the cross-linked phase so that a coating is formed issuitable to be used in the process according to the invention. Suitableways to initiate crosslinking are for example electron beam radiation,electromagnetic radiation (UV, Visible and Near IR), thermally and byadding moisture, in case moisture curable compounds are used. In apreferred embodiment crosslinking is achieved by UV-radiation. TheUV-crosslinking may take place through a free radical mechanism or by acationic mechanism, or a combination thereof. In another preferredembodiment the crosslinking is achieved thermally. Also combinations ofdifferent cure methods are possible.

Initiator

An initiator may be present in the mixture to initiate the crosslinkingreaction. The amount of initiator may vary between wide ranges. Asuitable amount of initiator is for example between above 0 and 5 wt %with respect to total weight of the compounds that take part in thecrosslinking reaction.

When UV-crosslinking is used, the mixture preferably comprises one ormore UV-photo-initiators. Any known UV-photo-initiators may be used inthe process according to the invention.

Coating Thickness

The coating according to the invention can be prepared in any desiredthickness. The coatings according to the invention typically have athickness ranging between 50 nm to tens of micrometers.

Substrates

A wide variety of substrates may be used as a substrate in the processaccording to the invention. Suitable substrates are for example flat orcurved, rigid or flexible substrates including films of for examplepolycarbonate, polyester, polyvinyl acetate, polyvinyl pyrollidone,polyvinyl chloride, polyimide, polyethylene naphthalate, polytetrafluoroethylene, nylon, polynorbornene or amorphous solids, for example glassor crystalline materials, such as for example silicon or galliumarsenide. Metallic substrates such as steel may also be used.

A free-standing coating obtainable by a process according to theinvention may be obtained by preparing a film or coating on a substrateand subsequently removing the film or coating from the substrate aftercrosslinking.

Application of the Mixture to a Substrate

The mixture may be applied onto the substrate by any process known inthe art of wet coating deposition in one or multiple steps. Examples ofsuitable processes are spin coating, dip coating, spray coating, flowcoating, meniscus coating, capillary coating and roll coating. An objectmay be totally coated or partially coated with the coating composition.Also partial crosslinking of the coating and removal of thenon-crosslinked part is possible, by for instance but not limited tophotolithography.

In a first embodiment the mixture according to the invention is appliedas the only coating on the substrate. In a second embodiment the coatingin applied on top of one or more coatings. Those versed in the art willknow which coatings to select to optimise properties such as adhesion,hardness, optical clarity etc.

After application and curing of the coating, further processing stepssuch as but not limited to a heat treatment or radiation treatment ispossible.

Solvent

The composition according to the invention may comprise a solvent, forexample to prepare a composition according to the invention that issuitable for application to the substrate using the chosen method ofapplication.

In principle, a wide variety of solvents may be used. The solventpreferably has the ability to form stable suspensions of the particlesgrafted with the reactive groups and the hydrophilic polymer chains, inorder to obtain good quality coatings i.e. after evaporation of thesolvent. The particles typically are added to the mixture in the form ofa suspension. The same solvent as used in the suspension may be used toadjust the mixture so that it has the desired properties. However, othersolvents may also be used.

Preferably the solvent used evaporates after applying the mixture ontothe substrate. In the process according to the invention, optionally themixture may after application to the substrate be heated or treated invacuum to aid evaporation of the solvent.

Examples of solvent that may be suitable are 1,4-dioxane, acetone,acetonitrile, chloroform, chlorophenol, cyclohexane, cyclohexanone,cyclopentanone, dichloromethane, diethyl acetate, diethyl ketone,dimethyl carbonate, dimethylformamide, dimethylsulphoxide, ethanol,ethyl acetate, m-cresol, mono- and di-alkyl substituted glycols,N,N-dimethylacetamide, p-chlorophenol, 1,2-propanediol, 1-pentanol,1-propanol, 2-hexanone, 2-methoxyethanol, 2-methyl-2-propanol,2-octanone, 2-propanol, 3-pentanone, 4-methyl-2-pentanone,hexafluoroisopropanol, methanol, methyl acetate, methyl acetoacetate,methyl ethyl ketone, methyl propyl ketone, n-methylpyrrolidone-2,n-pentyl acetate, phenol, tetrafluoro-n-propanol,tetrafluoroisopropanol, tetrahydrofuran, toluene, xylene and water.Alcohols, ketones and esters based solvents may also be used, althoughthe solubility of acrylates may become an issue with high molecularweight alcohols. Halogenated solvents (such as dichloromethane andchloroform) and hydrocarbons (such as hexanes and cyclohexanes), mayalso be suitable. Preferably methanol, methyl ethyl keton or isopropanolare used.

In a more preferred embodiment mixtures of organic solvents with waterare used. In the most preferred embodiment water is used as solvent.

Adhesion Promoters

Preferably the composition according to the invention comprises acompound that increases the adhesion of the coating to the substrate.These may be for example silane acrylate compounds for usage ofacrylate-containing coatings on glass. The skilled artisan will be ableto select a suitable adhesion promoter for the desired substrate.

Additional Additives

In a further embodiment the composition according to the invention maycontain one or more species that diffuse out of the coating duringusage. Such species may be used for lubricity, adhesional purposes orcomprise therapeutic species. Examples of such species are for instancebut not limited to heparin, vitamines, anti-inflamatory agents,antimicrobial functionalities such as quaternium ammonium ions, peptidesequences, halogen labile species etc., biomolecule receptor sites.

Post-processing steps, after the composition has been applied to thesubstrate may include: addition of migreatable species, for instancedrugs, via reversible sorption, or chemical grafting of bioactivespecies to remnant reactive groups in the coating.

The invention also relates to a film or coating obtainable from thecoating composition according to the present invention. The inventionalso relates to objects partly or in whole coated with the coatingcomposition according to the present invention.

The invention also relates to particles grafted with reactive groups andhydrophilic polymers as used in the composition according to theinvention.

Applications

Applications of the coating include coatings with anti-biofouling oranti-thrombogenic properties, coatings with anti-inflammatoryproperties, anti-microbial coatings, coatings to prevent biofilmformation, coatings for bioreceptors, coatings with anti-foggingproperties. It is also possible that the coating is applied to an objectto enhance wetting by aqueous solutions of the object.

The invention also relates to a process for producing the coatingcomposition according to the present invention comprising the step ofchemically grafting a hydrophilic chain to a particle.

With this process various coating compositions may be obtained, suitablefor all kind of applications.

EXAMPLES

The invention will be further explained by the examples, without beinglimited by that.

Materials Used in the Examples

A list of the materials used in the examples and their suppliers arereported in Table 1 and the properties of the nano-silicate particlesuspension (MT-ST) is listed in Table 2 below.

TABLE 1 Materials used in examples and their supplier. Material SupplierMono methyl ether polyethylene glycol Fluka (Mw 1100 g mol⁻¹) Monomethyl ether polyethylene glycol Fluka (Mw 2000 g mol⁻¹) Toluene MerckTriethoxy(3-isocyantopropyl)silane Sigma-Aldrich Dibutyltin dilaurateAldrich Silicon oxide nano particles in methanol Nissan Chemical (MT-ST)American Corporation Acrylpropyltrimethoxysilane (Acr-Pr-TMS) ABCRChemicals Hydroquinone monoethyl ether Sigma-Aldrich Trimethylorthoformate Sigma-Aldrich Methanol Merck Polyethylene glycol diacrylateSigma-Aldrich (Mw 248 g mol⁻¹) Irgacure 184 Ciba Chemicals

TABLE 2 Properties of dispersed silicon oxide nano particles. ParticleParticle Particle size/ SiO₂/ Viscosity/ Specific suspension shape nm wt% H₂O/% mPa · s gravity pH Solvent MT-ST Spherical 10-15 30.6 1.7 1.50.998 2-4 MethanolPreparation of mPEG Trimethoxysilane Polymer Chains.

Mono methyl ether polyethylene glycol (mPEG) (Mw=1100 and 2000 g mol⁻¹)was dissolved in toluene and the mixture was dried.

At room temperature and under nitrogen, a molar equivalent with respectto mPEG of triethoxy(3-isocyantopropyl)silane, was added drop wise tothe reaction mixture. As a catalyst a few drops of dibutyltin dilauratewere added, where after the reaction mixture was stirred continuouslyfor 24 hours at 50° C. The reaction was followed by infraredspectroscopy; the isocyanate signal occurs at ca. 2271 cm⁻¹. Uponcompletion, approximately two thirds of the toluene was removed byrotary evaporation and the mPEG trimethoxysilane was precipitated intohexane and washed several times. The resulting solid was dried andcharacterized by ¹H NMR. Reaction yields of >90% were obtained.

Preparation of the Particles Grafted with a Hydrophilic Polymer Chainsand Reactive Groups

Silicon oxide nano particles suspended in methanol (MT-ST) were graftedwith acrylpropyltrimethoxysilane (Acr-Pr-TMS) and one of the mPEGtrimethoxysilane polymers obtained as above, together with hydroquinonemonoethyl ether to inhibit the polymerization of the acrylate groups.

For preparing the silicon oxide nano particles, the above mentionedsilane compounds hydroquinone monoethyl ether were stirred together inan excess of water (with respect to the Acr-Pr-TMS concentration) andheated under reflux for two hours. Table 3 shows the exact amounts ofeach chemical used.

TABLE 3 Compounds in weight percentages used for the preparation ofhydrophilic reactive particles. Modified Modified Modified ModifiedSilicon Silicon Silicon Silicon oxide oxide oxide oxide nano nano nanonano Material particle A particle B particle C particle D MT-ST Silicon 27.0 wt % 25.65 wt % 26.14 wt % 26.4 wt % oxide nano particlesAcr-Pr-TMS  3.75 wt %  3.56 wt %  3.16 wt % 3.91 wt % mPEG  3.81 wt % 7.29 wt %  7.32 wt % — trimethoxysilane (Mw 1100 g mol⁻¹) mPEG — — —4.09 wt % trimethoxysilane (Mw 2000 g mol⁻¹) Hydroquinone  0.05 wt % 0.05 wt %  0.05 wt % 0.05 wt % monoethyl ether (inhibit polymerisation)Trimethyl  3.07 wt %  4.77 wt %  3.74 wt % 3.79 wt % orthoformate(dehydrating agent) Methanol 61.67 wt % 58.18 wt %  59.0 wt % 61.0 wt %(solvent) Water  0.65 wt %  0.50 wt %  0.59 wt % 0.55 wt % Total   100wt %   100 wt %   100 wt %  100 wt %

Examples 1-9 Preparation of Coated Substrates

Various formulations were prepared by mixing the modified silicon oxidenano particles A-D, according to Table 3 above, with a reactive diluent,polyethylene glycol diacrylate (Mw=248 g mol⁻¹), an adhesion promotercomprising Acr-Pr-TMS, and a photo initiator, Irgacure 184. The exactweights used for the formulations are shown in Tables 4 and 5.

Thin films of various formulations were prepared on glass microscopeslides (for measurements of wetting properties, nanoindentation) and onsilicon wafers with a 2.5 nm silica oxide layer (for measurements ofdurability, thickness determination and protein adsorption experiments).

A drop of the formulation (see Tables 4 and 5) was applied to thecleaned substrate and allowed to spin at a rate of 2000 r.p.m. for 20seconds. The resultant wet spin-coated samples were cross-linked with UVradiation using a D-bulb in an inert environment at a dose of ˜2.0J/cm². The coated substrates were then post baked (i.e. heated) byexposure to an IR lamp up to the temperature 120° C. and then placed inan oven at 70° C. for 12 hours.

Measurement of Static Water Contact Angle

Static contact angle measurements were measured of coatings according toexamples 1-6 using an apparatus comprising a syringe, sample stage andvideo camera. Images were analysed using Vision Gauge Software (standardedition, version 6.39).

Prior to the measurements, calibration of the camera and the surfacetension of the water in the syringe were measured. The latter wascarried out by dispensing a droplet of water from the syringe, and thenrecording the image whilst the droplet was still attached to thesyringe. The software measured the dimensions of the droplet and usedthem to calculate the surface tension.

The static contact angle of the samples was measured by dispensing a 50μl droplet of distilled water onto the surface of the coated substrate.Ten images of the droplet were taken over a 135 second period. From theimages, the software determined the baseline (the surface) and the edgesof the droplet; the contact angle was calculated where these linesintercept. After that the average value of the 10 images was calculated.The contact angles were determined for at least two droplets depositeddifferent areas of the surface.

Results of the static water contact angle for the coatings formulationson glass substrates according to Examples formulations 1-6 are reportedin Table 4.

TABLE 4 Example formulations for coatings prepared on glass substratesand their static water contact angle. Exam- Exam- Exam- Exam- Exam-Exam- ple 1 ple 2 ple 3 ple 4 ple 5 ple 6 Material g g g g g g Modified3.0 3.0 3.0 — — — Silicon oxide nano particle A Modified — — — 3.0 3.03.0 Silicon oxide nano particle D Polyethylene — 0.05 0.1 — 0.1 0.1glycol diacrylate Mw 248 g mol⁻¹ Acr-Pr-TMS 0.05 0.05 0.1 0.1 — 0.1Photo 0.002 0.002 0.002 0.002 0.002 0.002 initiator irgacure 184(trademark by Ciba) Water 18 12 31 32 27 26 contact angle after 135 s/°

TABLE 5 Example formulations for coatings prepared on silicon wafersubstrates with a 2.5 nm silica oxide layer. Example 7 Example 8 Example9 Material g g g Modified Silicon oxide 0.61 — — nano particle AModified Silicon oxide — 0.57 — nano particle B Modified Silicon oxide —— 0.52 nano particle C Acr-Pr-TMS 0.01 0.01 0.01 Methanol 2.79 2.79 2.82Water 6.50 6.53 6.58 Photo initiator Irgacure 0.02 0.02 0.02 184 100 wt% solution in methanol (trademark by Ciba)Durability Measurements

Coating formulations prepared on the Silicon wafers were deposited inwater at room temperature and visually inspected over time. The rankingwas performed after 14 days and their appearance is shown in Table 6. Itcan be seen that coatings retained their integrity after prolongedimmersion in water.

TABLE 6 Appearance of coatings after immersion for 14 days in water.Example Appearance 7 Intact 8 Intact 9 IntactNanoindentation Measurements

In order to measure the hardness of the coatings, nanoindentation wasperformed on several samples in the dry state. The reference materialsfor such indentations were polycarbonate and a typical UV-curablehard-coat comprising reactive nanoparticles.

The indentations were performed with a Micromaterials 600 using atypical SiN Berkovitch indenter. Indentation were made at 500 nm and 10measurements were made, which are averaged. The hardness and reducedmodulus of the coating are determined via the standard Oliver & Pharrmethod. In Table 7 these values are given.

It can be seen that the reduced modulus and hardness of the coatingscomprising hydrophilic reactive particles are in the same regime astypical values for UV-curable hard-coats and surpass those ofthermoplastic polymers.

TABLE 7 Hardness and Reduced modulus from nanoindentation results on drycoatings at 500 nm depth for Example formulations 3 and 6, referencehard-coat and reference polycarbonate. Coating Hardness (GPa) Reducedmodulus (GPa) Example formulation 3 0.72 +/− 0.02 13.0 +/− 0.5  Exampleformulation 6 0.49 +/− 0.02 8.0 +/− 0.3 Reference hard-coat 0.60 +/−0.02  7.0 +/− 0.13 Reference polycarbonate 0.17 +/− 0.02  2.1 +/− 0.42Protein Adsorption Measurements

Protein adsorption measurements on the coatings prepared on the siliconwafer were carried out by stagnation point flow reflectometry. Theinstrument set-up, described by Dijt et al. J. Colloids Surf. 51, 141(1990), consists of a polarized light from a He—Ne laser that isreflected by the coating at the Brewster angle in a hydrodynamicallywell-defined position (stagnation point) of the incoming fluid. Thedetector splits the reflected beam into its parallel (p) andperpendicular (⊥) components and the ratio S=I_(p)/I_(⊥) of therespective intensities is measured continuously. Adsorption of materialonto the coating interface results in a change, ΔS, and underappropriate conditions (e.g. coating thickness, adsorbed mass) theadsorbed amount, Γ, exhibits a good linear relationship according to:

$\begin{matrix}{\Gamma = {\frac{\Delta\; S}{S_{0}} \cdot Q_{f}}} & \lbrack 1\rbrack\end{matrix}$where S_(o) is the initial ratio prior to adsorption. The constant Q_(r)is referred to as the quality factor, has units mg m⁻², and is dependenton the optical system. This was evaluated using a computer programmewhere an optical model consisting of a layered matrix is used todescribe the system. The programme requires values of the coatingrefractive index, n, and thickness. These were determined by computernull ellipsometery (Sentech Instruments GmbH) at λ=632.8 nm andangle=70° and the values are reported in Table 8.

A protein solution of lysozyme (Aldrich, Lot 51K7028) (0.156 mg ml⁻¹) in10 mM sodium nitrate buffer (pH 6.2, 250 ml) was prepared. Lysozyme is asmall protein (Mw=15 kDa, pl=10.9) that is often used as a model instudies of electrostatic adsorption. Coatings were immersed in thebuffer solution prior to the protein adsorption measurements for atleast two minutes allowing the coating to equilibrate. All themeasurements were carried out using a flow rate of 1.0 ml min⁻¹ and theprotein sample was allowed to flow following approximately two minutesin the buffer solution flowing in the chamber. Once a plateau had beenreached following the introduction of the protein sample, the buffersolution was then allowed to flow. This allows any non-adsorbed proteinsto be washed from the coating. The average plateau values of theadsorbed amount of lysozyme protein following the flow of buffersolution, Γ^(pla), calculated from three separate samples are reportedin Table 8 for Examples 7-9. For comparison, a silicon wafer notcomprising a coating was tested too.

TABLE 8 Coating thickness, refractive index (determined byellipsometry), average Γ^(pla) values for films exposed to lysozymeprotein solution and then buffer solution for example formulations and areference silicon wafer with a 75 nm silica oxide layer values. AverageΓ^(pla) lysozyme protein Average Γ^(pla) with flow Coating Refractivelysozyme of buffer thickness/nm index, n protein/mg m⁻² solution/mg m⁻²Example 7 55.8 1.41 0.90 0.65 Example 8 64.4 1.47 0.44 0.28 Example 947.1 1.47 0.10 0 Silicon wafer 75 1.47 2.07 1.69 with a 75 nm silicaoxide layer

It can be seen that the coatings according to Examples 7-9 result in areduction in the amount of adsorbed lysozyme protein when compared withthe silicon wafer with a 75 nm oxide layer. It is also interesting tonote that a significant amount of protein is desorbed when the buffersolution is allowed to flow into the cell following the proteinsolution. Moreover, and in agreement with theoretical predications andexperimental observations, a decrease in the adsorbed amount of proteinis found with increasing the grafting density of mPEG silane on thesilicon oxide nano particles.

The invention claimed is:
 1. A process for producing a coating composition comprising the steps of: (a) providing particles, compounds comprising reactive groups, and compounds comprising hydrophilic polymer chains, and (b) separately chemically grafting (i) the compounds comprising the reactive groups, and (ii) the compounds comprising the hydrophilic polymer chains to the particles, wherein the hydrophilic polymer chains comprise at least an average of 5 monomer units of ethylene oxide or vinylpyrrolidone.
 2. The process of claim 1, wherein the compounds comprising reactive groups are capable of reaction with a substrate on which the coating composition is coated and/or with one another to form a cross-linked phase.
 3. The process of claim 1, wherein the particles are inorganic.
 4. The process of claim 1, wherein the average smallest diameter of the particles is below 10 micron.
 5. The process of claim 1, wherein the particles comprise SiO₂, TiO₂, ZnO₂, TiO₂, SnO₂, Am—SnO₂, ZrO₂, Sb—SnO₂, Al₂O₃, Au or Ag.
 6. The process of claim 1, wherein the hydrophilic polymer chains comprise monomer units of ethylene oxide.
 7. The process of claim 1, further comprising adding to the coating composition a compound that increases adhesion of the coating to the substrate.
 8. The process of claim 1, further comprising adding to the coating composition one or more species that diffuse out of a coating comprising the composition during usage.
 9. The process of claim 1, further comprising the step of adding to a coating composition one or more species to impart anti-biofouling or anti-thrombogenic properties to the coating composition during usage.
 10. A process for coating a substrate which comprises coating onto a surface of a substrate a coating composition as in claim
 1. 11. The process of claim 1, wherein at least 20% of the hydrophilic polymer chains do not comprise a reactive group.
 12. The process of claim 1, wherein at least 80% of the hydrophilic polymer chains do not comprise a reactive group.
 13. A coating composition produced by the process of claim
 1. 14. The coating composition of claim 13 wherein the coating composition is bioreactive.
 15. An article coated by the coating composition of claim
 13. 16. A process for coating an article comprising: (a) coating an article with the coating composition of claim 13, and (b) cross-linking the coating composition applied to the article.
 17. An article coated by the process of claim
 16. 